Diagnosis, misdiagnosis, and associated diseases of achalasia in children and adolescents: a twelve-year single center experience.

PURPOSE: Although achalasia is a rare disorder in children, its symptom may mimic common childhood diseases. This study aimed to assess the diagnosis and management of achalasia in children and adolescents in a Brazilian single center during a 12-year period. METHODS: Patients with achalasia were identified from a database built during the period of January 2000-January 2012 from a Pediatric Gastroenterology reference center. Information regarding demographic data, clinical symptoms, diagnosis, treatment, and long-term follow-up were described. RESULTS: Thirteen patients were studied; median age was 7 (1-14) years. Most frequent symptoms were vomiting (84.6 %) and dysphagia (69.2 %). Weight loss occurred in 46.0 % of patients and chronic cough in 46.1 %. Associated disorders were Down's syndrome, Allgrove syndrome, and congenital central hypoventilation syndrome. Achalasia was misdiagnosed with anorexia nervosa. Six patients were previously treated as having gastroesophageal reflux disease and asthma. Five patients had pneumatic balloon dilation as initial therapy whereas five had esophageal myotomy. Finally, 11 patients had surgical therapy with a favorable follow-up. CONCLUSION: Achalasia symptoms may mimic common diseases in children, and therefore, may delay the diagnosis. This study emphasizes the importance of the clinical symptoms for the diagnosis of achalasia, mainly in those cases with associated disorders.

Nocturnal reflux in children and adolescents with persistent asthma and gastroesophageal reflux.

BACKGROUND: A higher frequency of nocturnal gastroesophageal reflux (GER) in adult patients with respiratory symptoms has been demonstrated. The aim of this study was to determine the prevalence of nocturnal GER by using prolonged intraesophageal pH monitoring and compare it with spirometry results in children with persistent asthma. METHODS: Thirty-eight patients with persistent asthma for at least 2 years were studied. Gastrointestinal symptoms suggestive of GER were considered as regurgitation, heartburn, and abdominal pain. All patients underwent prolonged intraesophageal pH study and spirometry. GER was considered positive when a reflux index (RI) was higher than 5%. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV(1)), forced mid-expiratory flow rate (FEF(25-75%)), and FEV(1)/FVC ratio were measured. RESULTS: Median age was 10 years of age (range 5 to 15) and 58% were male; GER prevalence was 47.3%. Median (range) of reflux index during supine and upright periods from GER patients were, respectively, 8.7% (3.2 to 23.6) and 10.5% (5.2 to 15.0) (p = 0.913), and only FEF(25-75%) was below the predicted value: 54.5% (39.4 to 96.9). Reflux index was not significantly correlated with FVC, FEV(1) and FEF(25-75%). CONCLUSIONS: A high prevalence of GER was found in children and adolescents with persistent asthma, equally distributed in the supine (nocturnal) and upright positions. There was no correlation with pulmonary function test.

Endoscopic augmentation of the esophagogastric junction with polymethylmethacrylate: durability, safety, and efficacy after 6 months in mini-pigs.

BACKGROUND AND AIMS: Endoscopic augmentation of the esophagogastric junction (EGJ) with polymethylmethacrylate (PMMA) has been reported in an experimental short-term study. We assessed whether endoscopic augmentation of the EGJ with PMMA is durable, safe, and efficacious after 6 months in mini-pigs. METHODS: Ten mini-pigs were studied under anesthesia. After a pilot study in two animals, eight mini-pigs underwent lower esophageal sphincter (LES) manometry and gastrostomy with measurement of gastric yield volume (GYV) and gastric yield pressure (GYP). Endoscopic implantation of PMMA was performed aiming for the submucosa of the EGJ. Six months later, LES manometry and GYV and GYP measurements were repeated and animals were sacrificed, followed by microscopic analyses of the EGJ. RESULTS: Out of 32 implants (four per animal), 29 (91%) were identified as submucosal nodules postmortem. PMMA deposits were found at microscopic analysis in all animals and located as follows [mean (range)]: submucosa 61.5% (37.5-91%), muscularis propria 21.5% (0-58%), mucosa 11% (0-25%), and subserosa 6% (0-17%). Neither esophageal perforation nor death was observed. A significant increase in GYV (1,404 versus 905 ml; p = 0.02) and a borderline increase in GYP (8.1 versus 6.5 mmHg; p = 0.057) were detected 6 months later. CONCLUSIONS: Endoscopic augmentation of the esophagogastric junction with PMMA was durable and had no complications after 6 months. However, the occurrence of implants in the subserosa requires technical refinement before use in clinical trials.

Is ineffective oesophageal motility associated with reflux oesophagitis?

OBJECTIVE: To evaluate the association between ineffective oesophageal motility and reflux oesophagitis controlling for hiatal hernia, hypotensive lower oesophageal sphincter and male sex in patients with gastro-oesophageal reflux disease. METHODS: A total of 387 patients with reflux disease (mean age, 46 years, 42% men) were consecutively selected from a database. All patients underwent upper endoscopy, oesophageal manometry and 24 h oesophageal pH-metry in accordance with a standardized protocol. Reflux disease was confirmed either by endoscopy (oesophagitis grade I-IV according to Savary-Miller) or by pH-metry (increased acid exposure). Hiatal hernia was diagnosed endoscopically, whereas ineffective oesophageal motility and hypotensive lower oesophageal sphincter were characterized during manometry testing. The association between ineffective oesophageal motility and reflux oesophagitis was assessed by logistic regression analysis. RESULTS: A total of 166 patients with oesophagitis (mean age 45 years, 49% men) and 221 without oesophagitis (mean age 46 years, 37% men) were present. Prevalences of ineffective oesophageal motility, hiatal hernia, hypotensive lower oesophageal sphincter and male sex were significantly higher in patients with oesophagitis compared with those without oesophagitis (P<0.05). Ineffective oesophageal motility was independently associated with oesophagitis after multivariate logistic regression analysis (odds ratio=1.68; 95% confidence interval=1.04-2.70). CONCLUSION: Ineffective oesophageal motility is associated with reflux oesophagitis, independently of hiatal hernia, hypotensive lower oesophageal sphincter and male sex.

Acid and Weakly Acidic Gastroesophageal Reflux and Pepsin Isoforms (A and C) in Tracheal Secretions of Critically Ill Children.

BACKGROUND: Gastroesophageal reflux (GER) and pulmonary aspiration are frequent in patients in the ICU. The presence of pepsin in airways seems to be the link between them. However, pepsin isoforms A (gastric specific) and C (pneumocyte potentially derived) need to be distinguished. This study aimed to evaluate GER patterns and to determine the presence of pepsin A and C in tracheal secretions of critically ill children receiving mechanical ventilation. METHODS: All patients underwent combined multichannel intraluminal impedance-pH (MII-pH) monitoring. Tracheal secretion samples were collected to determine the presence of pepsin. Pepsin A and C were evaluated by Western blot. MII-pH parameters analyzed were number of total GER episodes (NGER); acid, weakly acidic, and weakly alkaline GER episodes; and proximal and distal GER episodes. RESULTS: Thirty-four patients (median age, 4 months; range, 1-174 months) were included. MII-pH monitoring detected 2,172 GER episodes (77.0% were weakly acidic; 71.7% were proximal). The median NGER episodes per patient was 59.5 (25th-75th percentile, 20.3-85.3). Weakly acidic GER episodes per patient were significantly more frequent than acid GER episodes per patient (median [25th-75th percentile], 43.5 [20.3-68.3] vs 1.0 [0-13.8], respectively; P < .001). Only three patients had an altered acid reflux index (44.9%, 12.7%, and 13.6%) while not taking antacid drugs. Pepsin A was found in 100% of samples and pepsin C in 76.5%. CONCLUSIONS: The majority of GER episodes of children in the ICU were proximal and weakly acidic. All patients had aspiration of gastric contents as detected by pepsin A in tracheal fluid. A specific pepsin assay should be performed to establish gastropulmonary aspiration because pepsin C was found in > 70% of samples.

Gastric yield pressure and gastric yield volume to assess anti-reflux barrier in a porcine model.

Anti-reflux barrier (ARB) resistance may be useful to test new treatments for gastroesophageal reflux (GER). The ARB has been estimated by increasing gastric yield pressure (GYP) and gastric yield volume (GYV) in animal models but has not been validated. This study aimed to develop an experimental model suitable for assessing the ARB resistance to increasing intragastric pressure and volume and its reproducibility in a seven-day interval. Ten two-month-old female Large-White swine were studied. Intragastric pressure and volume were recorded using a digital system connected to a Foley catheter inserted through gastrostomy into the stomach. GYP and GYV were defined as the gastric pressure and volume able to yield gastric contents into the esophagus detected by esophageal pH. A sudden pH drop below 3 sustained during 5 min was considered diagnostic for gastric yield. Animals were studied again after seven days. On days 0 and 7, there were no significant differences for GYP (mean ± SD = 7.66 ± 3.02 mmHg vs. 7.07 ± 3.54 mmHg, p = .686) and GYV (636.70 ± 216.74 ml vs. 608.30 ± 276.66 ml; p = .299), respectively. Concordance correlation coefficient (ρc) was significant for GYP (ρc = 0.634, 95% CI = 0.141-0.829, p = .006), but not for GYV (ρc = 0.291, 95% CI = -0.118 to 0.774, p = .196). This study demonstrated an experimental model, assessing the ARB resistance. GYP seems to be a more reliable parameter than GYV for assessment of ARB resistance.

Clinical outcomes of eradication of Helicobacter pylori in nonulcer dyspepsia in a population with a high prevalence of infection: results of a 12-month randomized, double blind, placebo-controlled study.

Ninety-one Helicobacter pylori-positive patients with nonulcer dyspepsia were randomized to receive either lansoprazole, amoxicillin, and clarithromycin or lansoprazole and placebo. A validated questionnaire assessed dyspeptic symptoms at baseline and at 3, 6, and 12 months. Endoscopies and biopsies were performed at baseline and at 3 and 12 months. There was an overall trend, although not statistically significant, for a benefit of H. pylori eradication. Of the patients in the antibiotics group, 16 of 46 (35%) had symptomatic improvement, versus 9 of 43 (21%) in the control group (P = 0.164). In a secondary analysis, it was found that of the patients without endoscopic gastric erosions, 15 of 34 (44%) in the antibiotics group and 5 of 33 (15%) of controls had symptomatic improvement (P = 0.015). Helicobacter pylori eradication did not prove to be clinically beneficial, although a tendency to symptomatic benefit was detected. Further studies are necessary to confirm the implications of endoscopic gastric erosions in these patients.

p53 immunoexpression: an aid to conventional methods in the screening of precursor lesions of squamous esophageal cancer in patients at high-risk?

INTRODUCTION: Squamous cell carcinoma of the esophagus (SCCE) is diagnosed late and carries a poor prognosis. Lugol chromoendoscopy (LC) has being shown a useful tool in the management of patients at high risk for SCCE. Biomarkers such as p53 protein expression may be present in the esophageal mucosa long before esophageal symptoms or lesions appear and may aid in early diagnosis. This study was carried out to investigate the p53 immunoexpression in esophageal mucosa of smokers and alcohol consumers and study its relationship with different degrees of histological findings and the role of LC to detect areas that express p53. METHODS: Group 1: One hundred and eighty-two asymptomatic subjects at high risk for SCCE (consumption of more than 80 g of ethanol and 10 cigarettes/day for at least 10 years). Group 2: Twenty healthy volunteers who neither smoked nor consumed alcohol. Both groups underwent upper GI endoscopy plus LC, with biopsies of the esophageal mucosa. Expression of p53 protein was compared to histological findings. RESULTS: Group 1: There was 25/182 (14%) Lugol's unstained areas. p53 protein was expressed in a stepwise fashion according to the severity of the histological findings: normal mucosa (12/103 or 12%), mild esophagitis (6/43 or 14%), moderate esophagitis (4/18 or 22%), severe esophagitis (1/3 or 33%), low-grade dysplasia (4/11 or 36%), high-grade dysplasia (2/2 or 100%) and squamous cell carcinoma (2/2 or 100%) (p=0.001). Nine in 25 (36%) patients with Lugol's unstained areas and 22/157 (14%) with normal appearing Lugol's stained mucosa expressed p53. Group 2: There was no Lugol unstained areas. The histological analysis and immunohistochemistry for p53 were normal with the exception of two patients that presented mild esophagitis and expressed p53. Unstained areas were 3.5 times (95% CI: 1.2-9.6) more likely to express p53 then stained ones. Alcoholics/smokers were 1.9 (95% CI: 0.4-8) times more likely to express p53 than non-alcoholics/non smokers. CONCLUSIONS: In this study, we find an association between histological alterations, p53 expression and Lugol's unstained areas. It may point to a higher risk for SCCE. Smokers and alcohol drinkers with normal mucosa or chronic esophagitis that express p53 protein may represent an unrecognized sub-group of individuals that may benefit from surveillance or intervention.

Compartmental analysis of ranitidine doubled peak plasma profile after oral administration to healthy volunteers

The aim of this study was to describe the double peak plasma pharmacokinetic profile of ranitine after oral administration to healthy volunteers using non-compartmental and compartmental analysis. A single 300mg dose of ranitide was given to ten healthy volunteers (5 male and 5 female). Blood samples were drawn at different times and analyzed by HPLC. Plasma profiles were evaluated by non-compartmental and compartmental approaches. The non-compartmental parameters determined were k (0.0054 ñ 0.0010 min-1), t 1/2 (2.2 ñ 0.4 h), Vd steady state/F (265.3 ñ 70.6L), Cl/F (84.8 ñ 24.3 L/h) and AUC (225916 ñ 54099 ng*min/mL)...